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New Insights Into Novel H1N1

This spring, a new influenza, or flu, virus began causing illness in people around the world. Originally called "swine flu" because it's a descendant of viruses that have long infected pigs, the virus is now called "novel H1N1." Several new studies have revealed where the virus came from and given insight into how dangerous it might become.

Influenza viruses have 8 genes, 2 of which—hemagglutinin
(H) and neuraminidase (N)—code for proteins on the virus
surface that allow the virus to enter and spread from cell to
cell. There are 16 H subtypes and 9 N subtypes, making 144 possible
HN combinations. Subtle variations in these 2 proteins affect
how easily the viruses infect people and whether the immune system
can recognize them.

Several research groups funded by NIH's National Institute of
Allergy and Infectious Diseases (NIAID) and National Institute
of General Medical Sciences (NIGMS) have recently put together
a picture of where the novel H1N1 virus came from and how it
evolved. They discovered that the novel H1N1 virus is a descendent
not only of swine viruses but also of the H1N1 virus that caused
the 1918 pandemic, which killed 40-50 million people worldwide.

"The 1918-1919 influenza pandemic was a defining event
in the history of public health," says NIAID Director Dr.
Anthony S. Fauci. "The legacy of that pandemic lives on
in many ways, including the fact that the descendents of the
1918 virus have continued to circulate for 9 decades."

In other work, 2 research groups—an NIGMS-funded team
at the Massachusetts Institute of Technology and researchers
at the Centers for Disease Control and Prevention (CDC)—recently
collaborated to test the ability of novel H1N1 to spread and
cause disease. They isolated viruses from 3 patients and infected
mice and ferrets. The results were published online ahead of
print on July 2, 2009, in Science.

The researchers found that, compared to seasonal H1N1 flu viruses,
the novel H1N1 viruses replicated to higher levels in lung tissue
and were also more deadly. The scientists also found the viruses
in the intestinal tracts of the ferrets, which might explain
reports of gastro-intestinal problems in some infected people.
However, the novel H1N1 viruses transmitted less efficiently
between ferrets in respiratory droplets than seasonal H1N1.

The binding of influenza viruses to their target cells is mediated
by hemagglutinin. The researchers found that the novel H1N1 hemagglutinin
binds to receptors in the human respiratory tract much less effectively
than other flu viruses that infect humans. However, flu viruses
can mutate rapidly, so the virus could potentially improve its
ability to bind.

The researchers also found that novel H1N1 doesn't have a version
of another gene called PB2 that has been associated with efficient
virus transmission. However, they point out that the virus could
acquire another version of the gene through mutation or by exchanging
genes with other influenza viruses.

These recent insights into how novel H1N1 arose and how it spreads
will be crucial for stopping a pandemic. "We need to pay careful
attention to the evolution of this virus," says Dr. Ram Sasisekharan,
who led the MIT research team.